A frequent and potentially fatal complication of head trauma is delayed pulmonary dysfunction, a disorder which bears many similarities to the lung injury characterizing the adult respiratory distress syndrome. Although mechanisms linking head trauma to lung injury have not been delineated, studies in animal models indicate that pulmonary intravascular mononuclear phagocytes may be important effector cells. Compelling evidence suggests that activation of pulmonary intravascular macrophages (PIMs) or their putative precursor, resident monocytes, by bacteria, endotoxin, or circulating particulates leads to oxygen radical- dependent elaboration of chemical mediators which initiate and amplify development of lung injury. Against this background, the proposed research will test key aspects of the working hypothesis that head trauma promotes adverse changes in the microvascular phagocytes which culminate in development of lung injury. A comprehensive experimental approach utilizing a model of controlled head injury in rats along with pulmonary mononuclear phagocytes in primary culture will address the following aims. Specific Aims 1 will determine in an intact rat model whether isolated head trauma (a) promotes infiltration of the pulmonary circulation with mononuclear phagocytes (b) engenders pulmonary will test the hypothesis that oxygen radical-dependent bacterial killing by intravascular mononuclear phagocytes is linked to induction of pathways leading to synthesis of injurious prostanoids. We will determine (a) pulmonary intravascular mononuclear phagocytes kill bacteria via an oxygen radical-dependent mechanism; (b) activation of an oxygen radical- dependent microbicidal mechanism is linked to induction of prostaglandin H synthase and elaboration of vasoactive prostanoids, and; (c) the cytokines IL-1, IL-6, and TNF increase oxygen radical-dependent bactericidal activity of mononuclear phagocytes and potentiate expression of injurious prostanoids. These studies will provide fundamental information regarding cellular and biochemical links between head trauma and lung injury. Additionally, understanding the mechanism by which activation of lung antimicrobial pathways promotes synthesis of injurious chemical mediators will facilitate development of therapeutic strategies to forestall lung injury without impairment of host microbial defense.